Our studies have focused on the effects of retinoids and tumor promoting agents on the cell surface. Retinoids were shown to enhance the adhesiveness of NIH 3T3 cells to plastic substrates coated with laminin in a reversible manner and with maximal effect at 48hr. Simultaneous with its effect on cell attachment retinoic acid (RA) caused a marked (70%) decrease in the uptake of inositol. The onset of RA inhibition of (3H)inositol uptake was rapid, with a 10-15% decrease after 2-3h and 60-70% at 16h of RA. A decrease in uptake was found as RA increased from 10-8 to 10-5 Molar (M) and was reversible 48h after RA removal. Further maximal effect on inositol uptake was dependent on RA treatment of the cells after they reached saturation density. RA inhibition of inositol uptake was also observed in 3T3-Swiss and Balb/3T3 cells but not in two virally transformed 3T3 cell lines, previously shown not to respond to RA by increased adhesion. Treatment of NIH 3T3 cells with phorbol 12-myristate 13-acetate (PMA) enhanced cell attachment to laminin and type IV collagen. The effect was dose-dependent, as early as 30 min. and reached a maximum at 2 hrs. These results suggest that PMA may enhance NIH 3T3 cell adhesion through effects on laminin and type IV collagen receptors. Retinoic acid, which itself requires at least 6 hours to show an effect on attachment, did not have any effect on cell attachment in 2 hours and, if anything, slightly inhibited PMA-enhanced cell attachment to laminin and type IV collagen substrates.